Disclosures: The authors report no relevant financial disclosures.
August 02, 2021
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HbA1c variability increases mortality risk in diabetes

Disclosures: The authors report no relevant financial disclosures.
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Adults with diabetes in Israel had an increased mortality risk with higher variability in HbA1c levels over a period of 5 years, according to a study published in Diabetes/Metabolism Research and Reviews.

In an analysis of data from nearly 300,000 adults with diabetes, HbA1c trends were also a predictor of mortality, with all adults with a decreasing HbA1c trend at greater risk for death and those 70 years or older with an increasing HbA1c trend also having a higher mortality risk.

Adults with diabetes, an HbA1c of greater than 7% and a decreasing HbA1c trajectory have higher mortality odds than those with a stable HbA1c trend. Data were derived from Cahn A, et al. Diabetes Metab Res Rev. 2021;doi:10.1002/dmrr.3485.

“These data highlight the importance of maintaining glycemic stability throughout the years and encourages physicians to consider the long‐standing glycemic burden of their patients when evaluating their prognosis,” Avivit Cahn, MD, an endocrinologist and attending physician in the diabetes unit, department of endocrinology at Hadassah Hebrew University Hospital in Israel, and colleagues wrote.

Researchers conducted a historical cohort observation study of 293,314 adults aged 35 to 89 years with diabetes listed at least four times in the Israeli National Diabetes Registry from 2012 to 2016 (median age, 68 years; 49.6% men). HbA1c values were obtained for each year to determine clusters. Mortality data were obtained from January 1, 2017, to December 31, 2019, from the national population register. A K-means clustering machine learning algorithm was used to select variables and classify participants into subgroups.

Of the study cohort, 54.8% had diabetes for more than 10 years and 25% used insulin. There were no hospital admissions during the study period for 62.1% of participants, whereas 11.1% had at least three hospital admissions. The median last HbA1c recorded was 7%.

Participants were divided into three age groups: 35 to 54 years, 55 to 69 years and 70 to 89 years. These groups were then divided into either a stable HbA1c cluster, an increasing HbA1c cluster or a decreasing HbA1c cluster based on year-to-year HbA1c trends. The stable cluster included 79% of those aged 70 to 89 years, 75% of adults aged 55 to 69 years and 67% of participants aged 35 to 54 years.

In all age categories, adults in the increasing or decreasing HbA1c cluster had a higher likelihood for mortality during follow-up than those in the stable cluster. HbA1c was a predictor for mortality in all age groups. The risk for mortality increased for participants with an HbA1c of 7% or lower in the decreasing cluster, and those with an HbA1c of greater than 7% in the increasing cluster (P < .01 for both).

Adults with an HbA1c of greater than 7% in the decreasing cluster had a higher risk for mortality in the 35-to-54-year age group (OR = 1.6; 95% CI, 1.1-2.3; P = .02), the 55-to-69-year age group (OR = 1.3; 95% CI, 1.1-1.5; P < .01), and the 70-to-89-year age group (OR = 1.4; 95% CI, 1.2-1.5; P < .01). Only adults in the oldest age group had a high mortality risk in the increasing HbA1c cluster. The association was significant for those with an HbA1c of 7% or less (OR = 1.4; 95% CI, 1.2-1.7; P < .01) and adults with an HbA1c greater than 7% (OR = 1.2; 95% CI, 1.1-1.3; P < .01).

“This may indicate the importance of glycemic control at [older] age too, though it is unclear why no excess mortality was noted in the lower age groups as well,” the researchers wrote.

Researchers noted several limitations to the study, including the availability of only one HbA1c measurement per year for each participant, the lack of data on comorbidities and blood pressure readings, and missing information on medication usage other than insulin.